Urinary antibiotics concentrations, their related affecting factors and infant growth in the first 6 months of life: A prospective cohort study.

Antibiotic exposure even in low-dose could have potential adverse health effects, especially during early life. There is a lack of data on antibiotic burdens in early infancy. We aim to assess antibiotic exposure in infants from birth to 6 months of age, their related affecting factors and the association between antibiotic exposure and infancy growth. Urine samples were collected at ages of 3 days, 42 days, 3 months and 6 months from 197 term-born Chinese infants. A total of 33 representative antibiotics were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urinary antibiotics were detectable in 69.4%, 63.2%, 75.0% and 84.3% of infants at ages of 3 days, 42 days, 3 and 6 months, respectively. The dominant antibiotic categories detected were: Preferred as Veterinary Antibiotics (PVAs), Human Antibiotics (HAs), and Veterinary Antibiotics (VAs). The detectable rates were 30.6%, 45.8%, 58.9%, and 81.4% for PVAs, 34.1%, 20.8%, 28.6%, and 45.1% for HAs, and 36.5%, 12.5%, 6.3%, and 5.9% for VAs, at age 3 days, 42 days, 3 and 6 months, respectively. Urinary concentrations of HAs and preferred as human antibiotics (PHAs) in newborns at age 3 days were not associated with maternal intrapartum antibiotic prophylaxis. Similarly, no associations were observed between urinary antibiotics concentration and antibiotics use in infants at age 42 days or 6 months. The numbers and concentrations of urine detectable antibiotics were similar between infants with exclusive breastfeeding and infants fed with formula or mixed-feeding at all ages of 42 days, 3 and 6 months. At age of 42 days, infants in the low tertile of total antibiotics concentration or with one antibiotic detected had higher weight-for-length Z score and greater head circumference, compared to infants with no antibiotics detected. No associations were found between urinary antibiotics and any of the infant anthropometric measures at age 6 months. In conclusion, urinary antibiotics were detectable in most infants during the first 6 months of life, and PVAs, HAs and VAs were the most commonly detected antibiotics. This suggested the possibility of a foods-originated antibiotics exposure in children. No strong nor consistent associations were found between urinary antibiotic concentration and infant growth at the first six months of life. Still, attention is needed on the adverse health effect of early life exposure to antibiotics in future studies.

Maternal blood concentrations of toxic metal(loid)s and trace elements from preconception to pregnancy and transplacental passage to fetuses.

Intrauterine exposure to heavy metals may adversely affect the developing fetus and health later in life, while certain trace elements may be protective. There is limited data on their dynamic fluctuation in circulating concentration of women from preconception to pregnancy and the degree of transplacental passage to fetus. Such information is critically needed for an optimal design of research studies and intervention strategies. In the present study, we profiled the longitudinal patterns and trajectories of metal(loid)s and trace elements from preconception to late pregnancy and in newborns. We measured whole blood metal(loid)s in women at preconception, 16, 24 and 32 weeks of gestation and in cord blood in 100 mother-newborn pairs. Our data showed that the mean concentrations of mercury (Hg), lead (Pb), rubidium (Rb), manganese (Mn), and iron (Fe) were lower during early-, mid-, and late-pregnancy than at preconception. Copper (Cu), and calcium (Ca) concentrations increased after pregnancy (Cu 798 versus 1353, 1488, and 1464 µg/L). Concentrations at preconception were correlated with those during pregnancy for all examined metal(loid)s. Maternal Hg, Pb, and Se concentrations at late-pregnancy were correlated with those in newborn cord blood in various degrees (correlation coefficients: Hg 0.66, Pb 0.29, Se 0.39). The estimated placental transfer ratio for toxic metal(loid)s ranging from 1.68 (Hg) to 0.18 (Cd). Two trajectory groups were identified for Hg, Pb, Cd, Se concentrations. Hg concentrations may be correlated with maternal education levels. The study is the first to present longitudinal circulating concentration trajectories of toxic metal(loid)s and trace elements from preconception to pregnancy stages. A high degree of transplacental passage was observed in toxic metals Pb and Hg which may pose hazards to the developing fetus.

The Study of Ginger-Derived Extracellular Vesicles as a Natural Nanoscale Drug Carrier and Their Intestinal Absorption in Rats.

Extracellular vesicles have been widely used in drug delivery systems and clinical studies as a new natural nanoscale drug carrier. Most of these studies focused on the extracellular vesicles from animals, but few involved in the extracellular vesicles from edible plants. This study was the first to explore the potential and value of ginger-derived extracellular vesicles (GDEVs) as drug carrier by using the content ratio method and to further study their intestinal absorption in rats. In this experiment, GDEVs were extracted and purified by ultrahigh-speed centrifugation. GDEVs were saucer-like with a particle size of 70.09±19.24 nm and a zeta potential of -27.70±12.20 mV. In this experiment, high-performance liquid chromatography was used to explore the difference in gingerol content between GDEVs and ginger slices. Under the same mass, the contents of 6-gingerol (6G), 8-gingerol (8G), and 10-gingerol (10G) in GDEVs were 10.21-fold, 22.69-fold, and 32.36-fold of those in ginger slices, respectively. In this experiment, the absorption kinetics and absorption site of GDEVs were investigated using in situ single-pass intestinal perfusion method in rats. GDEVs could be absorbed by the small intestine in the concentration range of 15-60 mg/mL, and the absorption trend of different intestinal segments was duodenum > jejunum > ileum. These results indicated that GDEVs had good loading capacity and significant prospects as a carrier of the drug delivery system. At the same time, combining the oil-water partition coefficient (6G < 8G < 10G) of three gingerol compounds, we speculated that the loading capacity of GDEVs increased with the increase of the lipid solubility of the compounds. This study fully demonstrated the potential and value of ginger-derived extracellular vesicles as natural nanocarrier and provided an important reference for the further application of plant-derived extracellular vesicles in the drug delivery system.

Mechanism and Application of Chitosan and Its Derivatives in Promoting Permeation in Transdermal Drug Delivery Systems: A Review.

The mechanisms and applications of chitosan and its derivatives in transdermal drug delivery to promote drug permeation were reviewed in this paper. Specifically, we summarized the permeation-promoting mechanisms of chitosan and several of its derivatives, including changing the structure of stratum corneum proteins, acting on the tight junction of granular layers, affecting intercellular lipids, and increasing the water content of stratum corneum. These mechanisms are the reason why chitosan and its derivatives can increase the transdermal permeation of drugs. In addition, various transdermal preparations containing chitosan and its derivatives were summarized, and their respective advantages were expounded, including nanoparticles, emulsions, transdermal microneedles, nanocapsules, transdermal patches, transdermal membranes, hydrogels, liposomes, and nano-stents. The purpose of this review is to provide a theoretical basis for the further and wider application of chitosan in transdermal drug delivery systems. In the future, research results of chitosan and its derivatives in transdermal drug delivery need more support from in vivo experiments, as well as good correlation between in vitro and in vivo experiments. In conclusion, the excellent permeability-promoting property, good biocompatibility, and biodegradability of chitosan and its derivatives make them ideal materials for local transdermal drug delivery.

Focusing on Future Applications and Current Challenges of Plant Derived Extracellular Vesicles.

Plant derived extracellular vesicles (EVs) are nano-sized membranous vesicles released by plant cells, which contain lipids, proteins, nucleic acids and specific pharmacologically active substances. They are safe, widely available and expediently extractive. They have gratifyingly biological activity against inflammation, cancer, bacteria and oxidative aging, especially for the prevention or treatment of colitis, cancer, alcoholic liver, and COVID-19. In addition, as natural drug carriers, plant derived EVs have the potential to target the delivery of small molecule drugs and nucleic acid through oral, transdermal, injection. With the above advantages, plant derived EVs are expected to have excellent strong competitiveness in clinical application or preventive health care products in the future. We comprehensively reviewed the latest separation methods and physical characterization techniques of plant derived EVs, summarized the application of them in disease prevention or treatment and as a new drug carrier, and analyzed the clinical application prospect of plant derived EVs as a new drug carrier in the future. Finally, the problems hindering the development of plant derived EVs at present and consideration of the standardized application of them are discussed.

Strategies and Mechanism in Reversing Intestinal Drug Efflux in Oral Drug Delivery.

Efflux transporters distributed at the apical side of human intestinal epithelial cells actively transport drugs from the enterocytes to the intestinal lumen, which could lead to extremely poor absorption of drugs by oral administration. Typical intestinal efflux transporters involved in oral drug absorption process mainly include P-glycoprotein (P-gp), multidrug resistance proteins (MRPs) and breast cancer resistance protein (BCRP). Drug efflux is one of the most important factors resulting in poor absorption of oral drugs. Caco-2 monolayer and everted gut sac are sued to accurately measure drug efflux in vitro. To reverse intestinal drug efflux and improve absorption of oral drugs, a great deal of functional amphiphilic excipients and inhibitors with the function of suppressing efflux transporters activity are generalized in this review. In addition, different strategies of reducing intestinal drugs efflux such as silencing transporters and the application of excipients and inhibitors are introduced. Ultimately, various nano-formulations of improving oral drug absorption by inhibiting intestinal drug efflux are discussed. In conclusion, this review has significant reference for overcoming intestinal drug efflux and improving oral drug absorption.